How Cell Biologists Work: Hari Shroff on making microscopes sharper, faster, and gentler (no apps or gadgets required)

Hari Shroff enjoys hiking.

Hari Shroff hiking

Hari Shroff is a Senior Investigator at the National Institute for Biomedical Imaging and Bioengineering (NIBIB) and the Chief of the Section on High Resolution Optical Imaging (HROI). Shroff and his team are closing the gap between (to paraphrase Hari’s own words) what is currently possible for cell biologists to see using a microscope, and the things they dream they might be able to see.

The Shroff Lab has developed microscopes and computational systems that allow biologists to visualize both the incredibly small and the lightning fast, two common “technical ceilings” cell biologists run up against when using traditional approaches. A consistent focus of the group’s effort has been pushing the boundaries of live cell imaging. The new microscopes designed by Shroff and his team, such as the diSPIM (Dual-View Inverted Selective Plane Illumination Microscopy) pictured below, allow cells and organisms, which tend to be sensitive to the large doses of intense light, to be imaged over extended periods at high temporal and/or spatial resolution.

The Shroff lab applies their innovative instruments to diverse organisms and biological questions, including mapping the formation of the C. elegans nervous system throughout embryonic development (Untwisting the Caenorhabditis elegans embryo, eLIFE), and they have recently been developing a high-speed TIRF (Total Internal Reflection Fluorescence) super-resolution microscope (see image below).

The microscopes designed in the Shroff Lab don’t look like the “off-the-shelf” varieties found in most biology labs and core facilities. The top images and left schematic are of the original variety of diSPIM scope designed by Shroff and his team. The bottom right schematic is a recent variation of the diSPIM that introduces a reflective coverslip to the mix, an innovation that gives additional information by providing views of the “other side” of a sample (this design is in press at Nature Communications).

 

A live U2OS cell expressing EGFP-HRas, imaged at 37C on a new, high speed TIRF super-resolution scope developed in my lab. Image was acquired in 48 ms by Min Guo and Panos Chandris.

 

Let’s start with your Name: Hari Shroff

Location: I live in Washington, DC, and work in the intramural research programs of the NIH at the Bethesda campus – specifically, NIBIB, or the National Institute for Biomedical Imaging and Bioengineering

Position: Senior investigator (i.e., tenured PI)

Current Mobile Device(s): Samsung Galaxy Note 4 smartphone – I was forced into this by my father, who gave it to me as a birthday gift last year, hoping I would use it to take photographs and send them to him. Before that, I had a ‘dumb’ flip phone. On balance I’d say I like the smartphone better, although it is easier to get distracted by it.

Current Computer(s): An HP Elitebook laptop (~2 years old)

What kind of research do you do?

I develop new optical microscopes that are sharper, faster, and gentler than those currently available—and I try to use these microscopes to study neurodevelopment in C. elegans embryos.

What is one word that best describes how you work:

Inefficiently 🙂 (but hard!)

What excites you most about your current work?

Being on the cutting edge and not knowing what we might discover.

Can you describe one experience from your life or training that set you on this path?

Doing undergraduate research—I owe a huge debt to my undergraduate advisor Jim Callis, who taught me that research could be exciting and rewarding. We worked on developing a phosphorescent paint for measuring the lift pressure of honeybees in hovering flight. The project ultimately failed, but I learned a lot and it was tremendously fun.

What is one part of your current position or project that you find challenging?

Some of the routine challenges are managing people (their personalities, and skillsets) and the emotional roller coaster of doing research. In one of my current projects imaging the worm embryo, a challenge is that the spatiotemporal resolution and optical sectioning is just not quite good enough, which is a good motivation for me to make better microscopes!

Do you have any specific advice about establishing or running a lab for new or aspiring faculty?

Make sure your hires are as good as possible and ignore the pressure to immediately fill the lab with bodies (which can be particularly difficult early on). Think carefully about projects before diving in, but take risks and don’t be afraid to plunge into the unknown. And as Bruce Lee said, ‘It’s not the daily increase but daily decrease. Hack away at the unessential’.

What is your approach to hiring people in your group? Do you value certain characteristics or past experiences highly?

I’ve found that hard work and motivation trump skillset most of the time. If there are particular projects I conceive that are well-matched to a particular scientific background I try to hunt for people with those skills, but otherwise, I try and go after people with passion.

Shroff’s office at the National Institute for Biomedical Imaging and Bioengineering

What’s your best time-saving shortcut/lifehack?

Making a list first thing in the morning and referring to it frequently throughout the day. Cycling my day between necessary but tedious busywork and fun activities like doing research with my lab.

What’s your favorite to-do list manager (digital or analog)?

The list I make every day in my lab notebook and google calendar.

What apps/software/language/tools can’t you live without?

I try not to use apps. I routinely use ImageJ/Fiji, and it would be hard to function without my laptop or email.

Besides your phone and computer, what gadget can’t you live without? And how do you use it?

Hmm, besides my phone and laptop, probably nothing – I try not to rely on gadgets.

What is one thing you never fail to do (in or outside of lab), no matter how busy you are?

Eat dinner with my wife.

Who is one of your scientific heroes, and what is one quality you admire in that person?

Dead: Richard Hamming. I’d recommend his article, You and Your Research. Living: Jeremy Nathans for his ability to give sound advice, and Erik Jorgensen for his obvious zest for life.

What do you like to read, learn, or think about outside of lab?

I like to read about the history of science, science fiction, dark/noir mystery, and nonfiction of all kinds.

Are there any causes or initiatives in or outside of science that you are particularly passionate about?

Spreading reason and educating the public about science are both important to me.

What are your favorite ways to go about educating this public about science?

I like to converse with the general public about my work and about science in general. I try to give as gifts books about the history of science to non-scientist friends. When I have the opportunity, I try to give “general science” talks to the public to explain why imaging brain development in worms is valuable beyond the developmental biology/imaging fields. Finally, I enjoy debating topics ranging from religion to free will with friends, acquaintances, and family.

What’s your sleep routine like?

I try to get at least 6.5-7 hours a night, consistently.

What’s the best advice you’ve received or some advice you’d like to share with trainees?

Eric Betzig once told me that failure should be the model in science, not success, and I agree entirely. In fact, I’ve pasted Samuel Beckett’s quote on the wall in front of my desk: “Try again. Fail again. Fail better.” Embrace failure! And learn from it!

 The views and opinions expressed in this blog are the views of the author(s) and do not represent the official policy or position of ASCB.

About the Author:


Jenny is a postdoc in John Rawls' laboratory at Duke University. She is currently studying host-microbe interactions in zebrafish. Twitter/Instagram: @hephephooray Email: jennyheppert@gmail.com